The long-term goal of this research is to test whether preclinical Alzheimer's disease (AD) is associated with impaired driving performance at baseline and at longitudinal follow-up. There is a long preclinical stage of AD, during which AD pathology is present without detectable cognitive or functional impairment. It is possible that preclinical A has subtle cognitive and functional effects which may combine to impair complex behaviors such as driving. This research is significant because 32 million licensed US drivers are aged 65 years or older, and the number of older adults in the U.S. is expected to double within the next 40 years, accompanied by a dramatic increase in the number of older adult drivers. The crash rate per miles driven is higher for older drivers; yet the mechanism behind this is not clear. The ability to identify who will be at most risk of decline in driving performance, forecast when decline will occur, document the type of impairment or decrement in traffic skills, and intervene before the time of decline, could prevent significant numbers of crashes, injuries with disabilitie, and deaths among our elders and the driving public. Achieving these aims could also prolong independence and a high quality of life for older adults. Our Specific Aims will move the field toward this goal by examining novel risk factors for driving decline among older adults: (1) We will determine, in 180 individuals aged 65 years and older with normal baseline cognition (Clinical Dementia Rating of 0), whether preclinical AD is a risk factor for impaired driving both at baseline and over 2-4 years of longitudinal follow-up. (2) In the same sample, we will determine whether cognitive and brain reserve factors are associated with driving performance both at baseline and longitudinal follow-up. (3) In the same sample, we will assess navigational skills to determine whether navigational impairments are risk factors for impaired driving both at baseline and longitudinal follow-up. To test these Specific Aims, we have assembled a multidisciplinary team with expertise in preclinical Alzheimer's disease, driving, cognitive and brain reserve, cognitive aging, neuroimaging biomarkers, cerebrospinal fluid (CSF) biomarkers and biostatistical methods. We will capitalize on our existing infrastructure to recruit participans who have valid driver's licenses and are currently driving at least one time per week. These participants will take part in updated measurement of amyloid imaging and cerebrospinal fluid biomarkers at baseline to establish the presence or absence of preclinical AD. Preclinical AD will be defined in several ways to help understand how the biology of preclinical AD may relate to impaired driving performance. Upon completion of this project, we will have valuable information regarding new important measures that have never been applied to the vital question of how to improve driving safety for older adults. PUBLIC HEALTH RELEVANCE: The long-term goal of this research is to test whether preclinical Alzheimer's disease is associated with impaired driving performance. Older drivers are at an increased crash rate per miles driven; yet the mechanism behind this is not clear. The ability to identify who will be at most risk of decline in driving performance, and to intervene before the time of decline, could extend driving privileges and prevent significant numbers of crashes, injuries with disabilities, and deaths among our elders and the driving public.